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Genetically Altered Skin Saves A Boy Dying Of A Rare Disease-转基因皮肤挽救了一个危在旦夕的男孩

In the future, we may not need to rely on human donations for life-saving skin grafts.

November 8, 20171:28 PM ET


Heard onAll Things Considered

That’s the goal of XenoTherapeutics, a Boston-based biotech nonprofit. Last week, the US Food and Drug Administration approved the group’s initial application for temporary skin grafts curated from genetically modified pigs. This means that they can start testing pig skin grafts on people who have experienced severe burns. It’s the first time that an animal organ has been cleared for human testing in the US.

Richard Harris


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Skin, the body’s largest organ, plays a crucial role in the immune system by blocking pathogens from reaching our vulnerable internal organs. It also holds in water, electrolytes, and other nutrients, and helps the body maintain a constant temperature. People with severe skin damage are at a high risk of developing deadly infections or organ failure as a result of changes in temperature or hydration.



grew sheets of genetically altered skin cells in the lab and used them

Skin grafts can help protect these patients as they heal. At the moment, the only skin grafts available in the US come from cadavers who have agreed to be organ donors, or patients who have undergone surgery to remove excess skin after dramatic weight loss. These human skin used for grafts are a “rare commodity.”

to treat a boy withlife-threatening epidermolysis bullosa.



XenoTherapeutics, which gets its name from xenotransplantation, or animal-to-human transplants, has bred pigs that have skin remarkably similar to our own. Although pig skin normally produces a type of sugar human skin does not, these pigs have been genetically modified not to make it. Grafts from these pigs are therefore more likely to slide under the radar of the host’s immune system—at least temporarily. The idea is that they could be used for immediate burn treatment, followed human skin graft treatment later.

CMR Unimore/Nature



“I would venture that if we did a Coke and Pepsi side-by-side comparison… you’d be hard-pressed to tell which was the human cadaveric allograft versus [the pig graft],” said XenoTherapeutics CEO Paul Holzer.

child who was on the verge of death from a rare inherited disease has


been treated with genetically engineered skin cells that replaced most

The nonprofit has been working closely with physicians at Massachusetts General Hospital, who will help conduct the clinical trials starting next month. The first trial will only be testing the grafts’ safety and tolerability in six patients with severe burns. Assuming the results are positive after a month, the grafts will need to undergo two more stages of testing before they can be approved for widespread clinical use.

of the skin on his body.



Several other groups around the world are working to make animal organs suitable for clinical medicine. In Brazil, researchers are exploring using tilapia skin for use as temporary bandages for burn victims whose skin is regrowing. Just last week, scientists from Germany reported that they had made a crucial step in keeping baboons given genetically modified pig hearts alive for half a year. Their success suggests that pig hearts could one day be used to treat patients with heart failure.



treatment represents a notable success for the field of genetherapy,

which has suffered manysetbacks. And it's potentially good news for

children suffering from a painful and often deadly skin condition called

epidermolysis bullosa.



this disease, children are born with a flawed gene that prevents the

outer layer of the skin, theepidermis, from binding to the inner layer.

This can cause excruciatingblistersto form all over these children's




the case in Europe, a 7-year old boy ended up in the hospital back in

2015 after 60 percent of his epidermis had sloughed off. Tobias

Rothoeft, a surgeon at a burn unit at Ruhr University in Bochum,

Germany, says he and his colleagues tried everything — including a skin

transplant from the boy's father —to no avail.

在欧洲的一个病例,一个7岁的男孩住进了医院,2015年后他的60%的皮肤已经脱落。Tobias Rothoeft,在波鸿的鲁尔大学的一名烧伤科医生德国说,他和他的同事们尝试了一切——包括男孩父亲的皮肤移植——但都无济于事。

"After nearly two months we were absolutely sure there was nothing we could do for this kid and that he would die," Rothoeft said in a telephone news conference hosted byNature, which publishedthe studyonline Wednesday.


Rothoeft and his colleagues took one last look around the medical literature and learned of researchers in Italy who were experimenting with anew treatment00126-4)for this disease. Michele De Luca and colleagues at the University of Modena and Reggio Emilia were genetically engineering skin cells to repair the inborn flaw.

Rothoeft和他的同事们偶然看到了一份医学文献,得知意大利的研究人员正在试验治疗这种疾病的新的治疗方法。来自意大利摩德纳大学Michele De Luca和科尔正利用基因工程的皮肤细胞修复基因的先天缺陷。


Luca used a virus toinserta healthy gene into cells taken from the

boy's skin. Some of those cells,stem cells,multiply indefinitely. So De

Luca was able to grow entire sheets of engineered epidermis, which were

shipped to the hospital in Germany.

De Luca用一种病毒将健康的基因插入从男孩皮肤中取出的细胞中。其中一些细胞,干细胞,无限期繁殖。所以De Luca能够一整面的转基因的人工表皮,它被运到了德国的医院。


Luca had used this procedure successfully in 2006 to replace a

relatively small patch of skin on another patient. But this boy needed

to have 80 percent of his skin replaced with grafts of this genetically

modified material. It took two operations, both in the fall of 2015.

De Luca在2006年成功地使用了这个办法来替换另一个病人的一小块皮肤。但是这个男孩需要80%的皮肤移植。在2015年秋季,他一共进行了两次手术。


the first one, we grafted all four limbs," De Luca told reporters in

the press call. "In the second operation we grafted the remaining part

of the body, mainly the back."

De Luca在接受记者采访时对记者说:“第一次,我们移植了所有四肢的皮肤。”在第二次手术中,我们移植了身体的剩余部分,主要是背部。


eight months in the intensive care unit, the boy was well enough to go

home. And, two years later, he is in school, even playing soccer.



kid is doing quite well," Rothoeft said. "The skin is of good quality,

it doesn't need any ointments or stuff like that. It's perfectly smooth

and it is quite stable. And if he gets any bruises, they

justheallikebruisesin every other kid."


Onelingeringquestion is the concern that gene therapies like this, involving viruses, can increase the risk of cancer. That's because the viruses insert the new gene randomly into human DNA. Anattemptat using gene therapy to treat severe combined immuneodeficiency (SCID) in 2002 ended up triggering cancer in some patients.


That bad result set back the field of gene therapy, though there have since been successes treatingSCID, and most recently, cancer.



it is a potential problem," De Luca said. But he generated hundreds of

millions of cells during this procedure and didn't see anything of

concern. And in this case, clearly the benefits of treating the boy

outweighed the risks.

“当然,这是一个潜在的问题,”De Luca说。但他在这个过程中产生了上亿的皮肤细胞,并没有发生任何令人担忧的事情。在这种情况下,显然治疗男孩的好处是远远大于风险的。

News of this is just starting to trickle out to advocates who have children with epidermolysis bullosa.


"I think it's groundbreaking," says Brett Kopelan, who heads a U.S. organization focused on this disease, known by its acronym,debra. "I think it's incredibly exciting."

“我认为这是开创性的,”关注这个疾病美国协会的负责人,Brett Kopelan说,“我认为这非常令人兴奋。”

His 10-year-old daughter Rafi has a severe case.


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Kopelan, 10, has epidermolysis bullosa, which causes painful blisters

of the skin and mucous membranes. Her father, Brett, is at right.

Rafi Kopelan,10岁,患有大疱性表皮松解症,导致痛苦的水泡性皮肤和粘膜。她的父亲,布雷特,在右边。

Courtesy of Brett Kopelan


the last time you had a paper cut and you put some Purell on it and it

stung, right?" Kopelan says. "Now imagine that being 60 percent of your




you have to do a bath and bandage change every day, you are subjected

to severe torture. It's incredibly painful, and it can take up to 3 to 4

hours a day," he says. "As a parent, there's not a day that goes by

that a little bit of my heart doesn't break.



Rafi, knowing that it's going to be an incredibly painful couple of

hours, walks into the bath and bandage room ... so that we can clean her

wounds to make sure they don't get infected and to prevent a

potentially life-threatening situation.


"She's the bravest person I know."



addition to the painfulblisters, Rafi needs frequent throat surgeries,

because her condition also affects mucous membranes. She often uses a

wheelchair because it's so painful to walk.



daughter would love to be able to not have to wear bandages on a daily

basis, she'd love to jump in a pool without worrying about it hurting,

or taking a shower — or even wearing shoes."


The skin therapy described in theNaturepaper wouldn't cure her — in fact, it targets a different genetic defect that causes the same condition. But a similar approach could reduce the agony of daily living. And Kopelan says medical interest in this disease is now growing rapidly.



gone from zero biotechnology and pharmaceutical [companies] to like 12

companies, so we're really at aninflectionpoint right now," he says.


Experimentaltreatments are getting under way in the United States and Asia, as well as in Europe. Peter Marinkovich, Jean Tang and colleagues at the Stanford University School of Medicine areusing the same approachas De Luca, and they have treated seven children using smaller patches of skin.

美国和亚洲以及欧洲正在进行实验性治疗。Peter Marinkovich,Jean Tang和他的同事们在斯坦福大学医学院使用和De Luca一样的方式,用小块皮肤治疗了七个孩子。


365游戏官方网站,tells Shots that their long-term goal is to treat a child's entire

body, and the research is gradually laying the groundwork to do that.

The severely injured child in Germany offered a unique opportunity to

try that, and the encouraging results are generating more enthusiasm. "I

was super impressed when I saw [the] results," Marinkovich says.



转基因皮肤挽救了一个危在旦夕的男孩,双语阅读。原文来自  NPRRichard HarrisNovember 8, 20171:28 PM ET